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Free Radic Biol Med. 2004 Dec 15;37(12):1921-42.

Metal-induced oxidative stress and signal transduction.

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  • 1National Institute for Occupational Safety and Health, Pathology and Physiology Research Branch, Health Effects Laboratory Division, 1095 Willowdale Road, MS/2015, Morgantown, WV 26505, USA.


Occupational and environmental exposures to metals are associated with the development of various cancers. Although carcinogenesis caused by metals has been intensively investigated, the mechanisms of action, especially at the molecular level, are still unclear. Accumulating evidence indicates that reactive oxygen species generated by metals may play an important role in the etiology of disease. This review covers recent advances in (1) metal-induced generation of reactive oxygen species; (2) the receptors, kinases, and nuclear transcription factors affected by metals and metal-induced oxidative stress, including growth factor receptors, src kinase, ras signaling, mitogen-activated protein kinases, the phosphoinositide 3-phosphate/Akt pathway, nuclear transcription factor kappaB, activator protein 1, p53, nuclear factor of activated T cells, and hypoxia-inducible factor 1; and (3) global cellular phenomena (signal transduction, cell cycle regulation, and apoptosis) associated with metal-induced ROS production and gene expression.

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